Osteopontin sequences modified mesoporous calcium silicate scaffolds to promote angiogenesis in bone tissue regeneration
Sufficient blood supply remains the key issue to be addressed for an optimal performance of implanted bone tissue engineering scaffolds. Host vessel invasion is limited to a depth of only several hundred micrometers from the scaffold/host interface. In this study, an osteopontin sequenced polypeptide SVVYGLR was grafted on mesoporous calcium silicate (MCS) and 3D-printed into scaffolds. The peptide motifs can be accessed on the scaffold surfaces. In vitro studies of human umbilical vein endothelial cells (HUVECs) indicated enhanced cell adhesion and vascular-like structure formation on MCS-SVVYGLR scaffolds. In the same time, human bone marrow stromal cells (hBMSCs) showed enhanced osteogenic differentiation capability and higher expressed level of angiogenic genes and proteins as well. In vivo radial defect repair tests of rabbits showed results that more tubular vessels formed throughout whole MCS-SVVYGLR scaffolds, and therefore, a more homogeneous new bone formation pattern was obtained on MCS-SVVYGLR scaffolds instead of peripheral bone growth pattern on pure MCS scaffolds by Micro-CT and tissue staining techniques over 3 months. Relative gene and protein expressions in PI3K/AKT and ERK1/2 pathways suggested SVVYGLR motif on MCS scaffold surface could initiate PI3K/AKT signaling pathway and up-regulated ERK1/2 expression, which positively stimulated VEGF expression, to improve angiogenesis.